Frances E. Lund, Ph.D.

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My laboratory studies the mechanism(s) that control inflammation in response to infectious, allergic and autoimmune diseases. In one project, we are examining the role that extracellular nucleotides play in regulating inflammatory processes. Our primary focus has been on CD38; an ectoenzyme that catabolizes extracellular NAD into three products that are each involved in calcium signaling. We previously showed that CD38, through the production of these calcium-mobilizing metabolites, regulates innate and adaptive immune responses by modulating signaling through chemokine receptors and controlling the trafficking of neutrophils, monocytes and dendritic cells to sites of inflammation and infection. Our current experiments address whether we can modulate cell trafficking and inflammation by manipulating extracellular NAD levels and whether changing the concentration of extracellular NAD impacts intracellular NAD levels, thereby affecting oxidative stress responses and metabolic fitness.

A second project in my laboratory focuses on immune and inflammatory responses to influenza virus. We know that antibodies and long-lived plasma cells play critical roles in immune protection from primary and secondary infections with influenza virus, yet we know very little about the factors that control the generation, maintenance and survival of the plasma cells, particularly within the local environment of the lung. To address these questions, we asked whether the factors that control the turnover and lifespan of memory B cells and plasma cells within primary and secondary lymphoid tissues also regulate B cells that reside in the lung. Interestingly, we found that while long-lived influenza specific plasma cells can remain in the lungs for life, the factors required to maintain these cells are distinct from those that control lifespan in the spleen and bone marrow. Our current goal is to identify the niches within the lung that can sustain plasma cells and determine how these niches are regulated both developmentally and in response to inflammatory signals.

The final project in my laboratory focuses on the antibody independent roles that B cells play in infection, autoimmune disease and cancer. We showed several years ago that B cells can produce different arrays of cytokines, depending on the environment in which the B cells were originally primed. These cytokine-producing "effector" B cells regulate the early innate immune response and also contribute to the adaptive immune response to pathogens. We are now focusing on using transcriptome and proteome analysis to phenotypically identify effector B cell subsets and to define different effector B cell "signatures" that can be used to identify these cells in peripheral blood. Using these signatures, we are now addressing whether any of the effector B cell subsets are inappropriately expanded or missing in autoimmune or cancer patients. Finally, we are asking whether specific depletion of different effector B cell subsets alters the course of disease in mouse models of cancer, autoimmune disease and infection.

Current Appointments

• Professor - Department of Medicine (SMD)
• Professor - Department of Microbiology and Immunology (SMD)

Lab Description

Lab goals are to understand inflammatory responses and determine how NAD-metabolizing enzymes regulate cellular responses and how B cells contribute to protection and pathology.

Lab Website

http://dev.mc.rochester.edu/medicine/allergy/research/LundLab.cfm